In the last few years, biomarkers have been used in basic and clinical research and their presence in primary endpoints in clinical trial is easily accepted. There are specific biomarkers that have been well characterised and repeatedly shown to correctly predict relevant clinical outcomes across a variety of treatments and populations but in many cases the validity of biomarkers should always be evaluated.
My aim in this article is to discuss the utility of biomarkers in different processes such as drug development.
A biomarker is a biological characteristic that is objectively measured and evaluated as an indicator of normal biological or pathological processes, or a response to a therapeutic intervention; examples include patterns of gene expression, levels of a particular protein in body fluids, or changes in electrical activity in the brain.
In the spring of 2015 the FDA-NIH Joint Leadership Council worked together to harmonize terms used in translational science and medical product development as a priority need, with a focus on terms related to study endpoints and biomarkers. Their aim was to improve communication, align expectations, and improve scientific understanding. The two agencies developed the BEST (Biomarkers, EndpointS, and other Tools) Resource.
Biomarkers can be included in seven categories:
- susceptibility/risk biomarker
- diagnostic biomarker
- monitoring biomarkers
- prognostic biomarker
- predictive biomarker
- pharmacodynamic/response biomarker
- safety biomarker
Clinical endpoints or surrogate endpoints?
As Dr Timbu and Dr Tavel said: "Biomarkers play a critical role in improving the drug development process as well as in the larger biomedical research enterprise. Understanding the relationship between measurable biological processes and clinical outcomes is vital to expanding our arsenal of treatments for all diseases, and for deepening our understanding of normal, healthy physiology."
For around 40 years, clinicians and researchers have been discussing the importance of using biomarkers as surrogate outcomes in large trials of major diseases, such as cancer.
To evaluate a biomarker, researchers and clinicians must completely understand the normal physiology of a biological process, the pathophysiology of that process in the disease state, and effects of a pharmacological intervention on these processes.
Unfortunately, these processes are hard to be figured out completely and biomarkers as surrogate endpoints need to be always reevaluated. Besides, studies using biomarkers should always have as final measures clinical outcomes correlation success, at least for retrospective analysis of biomarkers. A regular reevaluation of the relationship between surrogate endpoints and true clinical endpoints has to be done otherwise the drug might either harm the patient or can be inefficient.
In 2012, in Oxford Global's 7th Annual Biomarkers Congress, held in Manchester, England, researchers and clinicians focused on all types of biomarkers and their application (for example, prognostic and diagnostic markers, predictive markers, patient selection strategies in drug development, point-of-care solutions, pharmacodynamics and target engagement biomarkers as well as safety-related approaches). But two specific fields were important: oncology and inflammatory diseases, This is because they provided best case studies for biomarker discovery and clinical utility.
Since then, emerging biomarkers in these therapeutic areas have increased.
How are biomarkers emerging?
I will expand on only a few examples of the use of biomarkers in personalized cancer immunotherapy, in diagnostics and therapeutics and prognostic:
Dr Joyce El Hokayem